Major genetic components underlying alcoholism in Korean population
Major genetic components underlying alcoholism in Korean population
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DOI：
10.1093/hmg/ddm357
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发表时间：
2008-03-15
影响因子：
3.5
通讯作者：
Shin, Hyoung Doo
中科院分区：
文献类型：
--
作者：
Kim, Dai-Jin;Choi, Ihn-Geun;Shin, Hyoung Doo
酒精代谢是一种生物学决定因素，酒精代谢基因的遗传多态性对酒精代谢有重要影响。醇脱氢酶（ADH）将醇转化为乙醛，醛脱氢酶（ALDH）将乙醛转化为乙酸。ADH 1B（His 47 Arg）和ALDH 2（Glu 487 Lys）的基因多态性分别对酒精和乙醛的代谢率有显著影响。ADH 1B的保护性等位基因（ADH 1B * 47 His）编码快速乙醇代谢酶，而ALDH 2的敏感性等位基因（ALDH 2 * 487 Lys）与乙醛代谢速率降低密切相关。然而，这两种功能多态性的组合遗传效应尚未阐明。对韩国人群（n = 1，032）中两种多态性的联合分析显示，酒精中毒风险具有显著的遗传效应。在两个基因座上都携带易感等位基因的个体与同时携带两个保护等位基因的个体相比，酗酒的风险高91倍[比值比（OR）= 91.43，P = 1.4 x 10（-32）]，而在任一基因座上都携带一个易感等位基因和一个保护等位基因的个体与同时携带两个保护等位基因的个体相比，酗酒的风险高11倍（OR = 11.40，P = 3.5 x 10（-15））。这些遗传因素的可归因分数，基于人群对照计算，表明86.5%的酒精中毒患者中的酒精中毒可归因于韩国人群中ADH 1B * 47 Arg和/或ALDH 2 * 487 Glu的有害作用。
Alcohol metabolism is one of the biological determinants that could significantly be influenced by genetic polymorphisms in alcohol-metabolism genes. Alcohol dehydrogenase (ADH) converts alcohol to acetaldehyde, and aldehyde dehydrogenase (ALDH) converts acetaldehyde to acetate. The well-known genetic polymorphisms in ADH1B(His47Arg) and ALDH2(Glu487Lys) have dramatic effects on the rate of metabolizing alcohol and acetaldehyde, respectively. The protective allele of ADH1B (ADH1B*47His) encodes for a rapid ethanol-metabolizing enzyme, and the susceptible allele of the ALDH2 (ALDH2*487Lys) is strongly associated with decreased rate of metabolizing acetaldehyde. However, the combined genetic effects of both functional polymorphisms have not been clarified. The combined analysis of two polymorphisms among a Korean population (n = 1,032) revealed dramatic genetic effects on the risk of alcoholism. Individuals bearing susceptible alleles at both loci have 91 times greater risk for alcoholism [odds ratio (OR) = 91.43, P = 1.4 x 10(-32)] and individuals bearing one susceptible and one protective allele at either loci have 11 times greater risk (OR = 11.40, P = 3.5 x 10(-15)) compared with subjects who have both protective alleles. The attributable fraction of those genetic factors, calculated based on population controls, indicates that alcoholism in 86.5% of alcoholic patients can be attributed to the detrimental effect of ADH1B*47Arg and/or ALDH2*487Glu in Korean population.